Corey–Itsuno reduction

Corey–Itsuno reduction, also known as the Corey-Bakshi-Shibata (CBS) reduction, is a chemical reaction used in organic chemistry for the enantioselective reduction of ketones to secondary alcohols. This reaction employs a chiral oxazaborolidine catalyst, which was first reported by E.J. Corey and X-M. Cheng in 1987, and independently by Itsuno and co-workers. The catalyst is derived from proline, a naturally occurring amino acid, and is used in conjunction with borane (BH3) or its derivatives for the reduction process. The Corey–Itsuno reduction has become a fundamental tool in the synthesis of chiral molecules, particularly in the pharmaceutical industry, where the production of enantiomerically pure substances is crucial.

Reaction Mechanism

The mechanism of the Corey–Itsuno reduction involves the formation of a chiral oxazaborolidine catalyst from a proline derivative and a borane source. This catalyst complex then facilitates the reduction of the ketone to an alcohol, with the transfer of hydrogen atoms occurring in a manner that produces a high enantiomeric excess (ee) of the desired alcohol. The stereoselectivity of the reaction is determined by the chiral environment created by the oxazaborolidine catalyst, which directs the addition of hydrogen to the ketone in a preferential manner.

Applications

The Corey–Itsuno reduction has found widespread application in the synthesis of chiral alcohols, which are important building blocks in the production of various pharmaceuticals, agrochemicals, and natural products. Due to its high enantioselectivity, the reaction is particularly valuable in the synthesis of drugs that require a specific enantiomer for their biological activity.

Advantages

One of the main advantages of the Corey–Itsuno reduction is its high level of enantioselectivity, allowing for the production of enantiomerically pure alcohols. Additionally, the reaction conditions are generally mild, and the catalyst can be easily prepared from readily available materials. This makes the Corey–Itsuno reduction an attractive option for the synthesis of complex chiral molecules.

Limitations

Despite its many advantages, the Corey–Itsuno reduction does have some limitations. The reaction is primarily applicable to the reduction of ketones, and its use with other functional groups may not be as effective. Additionally, the cost of the chiral catalyst and the need for its careful preparation can be drawbacks in some applications.

See Also

• Enantioselective synthesis
• Chiral auxiliary
• Organic reduction
• Borane